1. Field of the Invention
The invention relates in general to the field of microfluidic surface processing devices as well as related methods.
2. Description of Related Art
Microfluidics generally refers to microfabricated devices, which are used for pumping, sampling, mixing, analyzing and dosing liquids. Prominent features thereof originate from the peculiar behavior that liquids exhibit at the micrometer length scale. Flow of liquids in microfluidics is typically laminar. Volumes well below one nanoliter can be reached by fabricating structures with lateral dimensions in the micrometer range. Reactions that are limited at large scales (by diffusion of reactants) can be accelerated. Finally, parallel streams of liquids can be accurately and reproducibly controlled, allowing for chemical reactions and gradients to be made at liquid/liquid and liquid/solid interfaces. Microfluidics is accordingly used for various applications in life sciences.
For example, inkjets were designed to deliver ink in a non-contact mode but not in the presence of a liquid. Other techniques can further pattern surfaces at higher resolution but are limited in their ability to operate in a liquid environment. Liquid environments minimize drying artifacts, denaturation of biomolecules, and enable working with biological specimens as cells or tissues.
For patterning surfaces and analyzing samples on a surface in the presence of a liquid environment, several strategies were developed to overcome limitations of closed microfluidics. Some strategies rely on confining liquids near a surface or, still, delivering a precise amount of biomolecules in a well defined region of a liquid. Scanning nanopipettes and hollow probes (resembling probes used in Atomic Force Microscopy) were also developed for patterning biomolecules on surfaces with micrometer accuracy.
As another example, a non-contact microfluidic probe technology (or “MFP”) was developed (see e.g. US 2005/0247673), which allows to pattern surfaces by adding or removing biomolecules, create surface density gradients of proteins deposited on surfaces, localize reactions at liquid interphases in proximity to a surface, stain and remove adherent cells on a surface, amongst other applications.
In another technical field, scanning probe microscopy (or SPM) was born with the invention of the scanning tunneling and the atomic force microscope. In brief, it aims at forming images of sample surfaces using a physical probe. Scanning probe microscopy techniques rely on scanning such a probe, e.g. a sharp tip, just above or in contact with a sample surface whilst monitoring interaction between the probe and the surface. An image of the sample surface can thereby be obtained. Typically, a raster scan of the sample is carried out and the probe-surface interaction is recorded as a function of position. Data are thus typically obtained as a two-dimensional grid of data points. The resolution achieved varies with the underlying technique: atomic resolution can be achieved in some cases. Typically, either piezoelectric actuators or electrostatic actuation are used to execute precise motions of the probe.
Two main types of SPM are the scanning tunneling microscopy (STM) and the atomic force microscopy (AFM). The invention of STM was quickly followed by the development of a family of other similar techniques (including AFM), which together with STM form the SPM techniques. Incidentally, the “probe” or “probe tip” used in SPM techniques should be distinguished from the “probe” as meant in MFP; the two types of probes differ functionally, structurally and dimensionally from each other.
Amongst SPM techniques, thermal probe-based techniques are known, which operate in air but are not suitable for operation in liquids. They further are limited to thermal activation of existing functional units at the processed surface. Among AFM techniques, one may for example cite:    “Applications of dip-pen nanolithography” (K. Salaita et al. Nature Nanotech., 2007, 2, 145-155); and    “Nanofountain-Probe-Based High-Resolution Patterning and Single-Cell Injection of Functionalized Nanodiamonds” (Loh, O., et al., Small, 2009. 5: pp 1667-1674).
Dip-pen is operating in air and generates drying artifacts. The Nanofountain probe is operating in liquid. It can basically be regarded as a micro-scale pipette. The processing liquid can diffuse away from the point of interest and can contaminate the surrounding liquid. Thus, it can be realized that with the above techniques, in situ operation in buffer solutions with sub-micrometer precision, is not possible. There is accordingly a need for high resolution surface processing devices that can easily be operated in a liquid environment.